Page 56 - M. Immunology

[M. Immunology-34]

Overexpression of p190RhoGEF in macrophage enhances the

formation of atherosclerotic plaques in mouse aorta

Eun Bi Lee¹, Jong Ran Lee²˙*

¹Department of Bioinspired Science, The Graduate School, Ewha Womans University, Seoul 03760, South Korea,

²Department of Life Sciences, College of Natural Sciences, Ewha Womans University, Seoul 03760, South Korea

Our laboratory has identified p190RhoGEF as one of the molecules, expression of which was increased after CD40
stimulation in B cells. Previous works in our laboratory showed that overexpression of p190RhoGEF affects B cell

maturation and differentiation. In addition, our studies also showed that p190RhoGEF overexpression affects

negatively in several functions of dendritic cells and macrophages in response to lipopolysaccharides (LPS). To study
whether overexpression of p190RhoGEF in macrophage affects mouse aortic atherosclerotic plaque formation, ApoE-
/- mouse was cross-bred with p190RhoGEF transgenic (TG), mouse in which p190RhoGEF is overexpressed in

macrophage. In this mouse model, aortic atherosclerotic plaques were increased rapidly up to 30 weeks, but
sustained and appeared to decrease afterwards. In contrast, plaque formation was slowly built in ApoE-/- aorta. To

explain these phenomena, level of serum cytokines (IL-6, TNF-α) and M1 macrophage population, as well as,
macrophage functions (IL-6 secretion and reactive oxygen species production) in response to LPS were analyzed.

The results from these studies partly suggest that increase in M1 population and serum cytokine level may be
responsible for rapid atherosclerotic plaque formation observed in TG/ApoE-/- mice.